Primary necrotizing lymphocytic central nervous system vasculitis due to perforin deficiency in a four-year-old girl

Arthritis Rheum. 2007 Mar;56(3):995-9. doi: 10.1002/art.22442.


We report the case of a 4-year-old girl who presented with headaches, ataxia, and visual disturbances. Cranial magnetic resonance imaging showed multiple supra- and infratentorial lesions with peripheral contrast enhancement and central necrosis. Brain biopsy revealed necrotizing lymphocytic vasculitis of undetermined etiology. Perforin expression was found to be significantly reduced in the patient's peripheral blood cells, and sequence analysis of the patient's perforin gene showed a compound heterozygous state with 1 nonsense mutation and 2 missense alterations in exon 2. Central nervous system (CNS) vasculitis was thus attributed to the perforin deficiency, and the patient was successfully treated by transplantation of stem cells from an HLA-identical brother. The findings described herein indicate that, even in the absence of classic non-neurologic symptoms of hemophagocytic lymphohistiocytosis, measurement of perforin expression should be one of the diagnostic tests used to identify the cause of unexplained CNS vasculitis, since this may have profound implications regarding therapy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Diagnosis, Differential
  • Female
  • Humans
  • Lymphocytes / pathology*
  • Lymphohistiocytosis, Hemophagocytic / diagnosis
  • Lymphohistiocytosis, Hemophagocytic / pathology
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Metabolic Diseases / complications*
  • Metabolic Diseases / diagnosis
  • Mutation / genetics
  • Necrosis
  • Perforin
  • Pore Forming Cytotoxic Proteins / deficiency*
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / metabolism
  • Vasculitis, Central Nervous System / diagnosis
  • Vasculitis, Central Nervous System / etiology*


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin